Conservationists fear that horseshoe crabs, a 450-million-year-old living fossil, will be pushed to the brink of extinction because of the value of their blood to the pharmaceutical industry. Horseshoe crab blood provides a natural source of limulus amebocyte lysate (LAL) which is used to test vaccines, drugs, and medical devices to ensure that they aren’t contaminated with dangerous bacterial toxins called endotoxins. With hundreds of thousands of horseshoe crabs captured and bled of their milky-blue blood each year, conservation groups are now stepping up their advocacy efforts and taking legal action to help save horseshoe crabs and the other species that rely on them.
Fortunately, there’s already an alternative to horseshoe crab blood: in the late 1990s, biologists at the University of Singapore created a synthetic version of the LAL called recombinant Factor C (rFC). Multiple studies show that rFC is just as effective as horseshoe crab-derived LAL, and it is currently commercially available.
Some 60 countries have approved rFC for use, including the EU countries and China. But in the US, conservationists were dealt a setback last year when Maryland-based US Pharmacopeia (USP), an organization that sets guidelines for the pharmaceutical industry, decided it needed to see more data before it would put rFC on equal footing with LAL. Companies can still opt to use rFC as a substitute for LAL (Eli Lilly already does) — but only if they go through additional bureaucratic processes first. Many environmentalists see the lack of approval by USP as short-sighted and unwise.
“We’re going to live in a world where we have more and more pathogens and the trend is for more pharmaceuticals requiring endotoxin testing,” says Ryan Phelan, executive director and co-founder of the environmental nonprofit Revive & Restore. “At some point, that’s going to put pressure on the supply of a non-sustainable product. Why would you not ensure your supply line?”
The global pharmaceutical and medical industry uses LAL to make sure that vaccines and a wide variety of medical devices and products are free from endotoxin contamination, which can cause fever, anaphylactic shock, and diseases like the bubonic plague. During testing, LAL clots around endotoxins, flagging their presence and quantifying the level of contamination. High demand for the compound can cause a quart of LAL to sell for $15,000 or more.
As a result, the business of bleeding horseshoe crabs is thriving. Today, American biomedical companies capture some 500,000 horseshoe crabs a year, a practice overseen by the Atlantic State Marine Fisheries Commission. But there are few laws or regulations in place to protect or limit the take of horseshoe crabs. And although the horseshoe crabs are eventually returned to the sea, conservation groups estimate that up to 30 percent of them die in the process. Due to pressure from the biomedical industry, along with habitat loss and the harvest of horseshoe crabs by commercial fishermen to use as bait, populations both in the US and worldwide have plummeted in recent decades.
In the Delaware Bay, home to the largest population in the US, horseshoe crab numbers have declined from 1.24 million in 1990 to less than 334,000 in 2002. Although the population appears to have stabilized, conservationists worry that increased demand for American horseshoe crab blood by the pharmaceutical industry could force it to go the way of the Asian horseshoe crab, Tachypleus tridentatus, which is rapidly disappearing in China and which the International Union for Conservation of Nature (IUCN) lists as endangered. Currently, the American horseshoe crab is listed as a vulnerable species.
Relying on horseshoe crabs for pharmaceuticals has knock-on effects to other species. As part of the bleeding process, Charles River Laboratories, one of the primary producers of LAL, sequesters crabs in holding pens away from the beach from May to June — the season when they lay eggs. During that window, a female horseshoe crab can lay as many as 80,000 eggs. Environmentalists contend that removing horseshoe crabs from the beach decreases the availability of horseshoe crab eggs as a food source for shorebirds such as the migratory red knot. The population of red knots, a threatened species under the Endangered Species Act, has dropped 80 percent in recent decades. Conservationists maintain that this decline is linked to a diminished supply of horseshoe crab eggs.
As a result of this linkage, the environmental nonprofits Defenders of Wildlife and the Coastal Conservation League recently notified the South Carolina Department of Natural Resources and Charles River Laboratories of their intent to sue both entities for alleged violations of the Endangered Species Act. The lawsuit seeks to protect the red knot’s food source and habitat by asking the state to end Charles River Labs’ practice of penning horseshoe crabs.
“The ponds maintained by agents of Charles River Labs further imperil the existence of red knots, a species whose fate already hangs in the balance,” Lindsay Dubin, staff attorney for Defenders of Wildlife, tells The Verge.
South Carolina’s Department of Natural Resources declined to comment on the lawsuit. Charles River Labs declined to provide specific responses about their horseshoe crab penning practices or its effect on red knot populations. Sam Jorgensen, a spokesperson for Charles River Labs, wrote in an email statement to The Verge that the company doesn’t see merit in the lawsuit and that it has taken strides to “protect and preserve a healthy and growing horseshoe crab population,” including by supporting an effort to ban the use of horseshoe crabs as fishing bait in eel and whelk fisheries. Jorgensen also noted that horseshoe crabs play a “vital role” in the healthcare system and that synthetic alternatives to LAL are “not readily available” or FDA-approved.
But despite the bureaucratic obstacles that currently stand in the way of widespread adoption of rFC in the US, advocates continue to urgently press for a switch away from a reliance on horseshoe crab blood. In addition to being more humane, rFC is lab-produced, so companies don’t have to worry about variance in the size of individual crabs or changes in their population, factors that can affect the production of LAL. If demand increases, manufacturers could produce more rFC at scale, which could lower the cost of production and make it less expensive. Critics of rFC like Charles River Laboratories — which, notably, stands to lose business if rFC becomes more widely used — maintain that rFC needs further study and testing to prove that it is completely safe and fully establish its efficacy.
The debate is particularly critical today; the COVID-19 pandemic has fueled a huge surge of research into vaccines and potential COVID-19 treatments which rely on the use of LAL to ensure product safety. As demand for vaccines and other medical products increases, conservationists worry that without a rapid switch to rFC, strain on the American horseshoe crab and the other creatures that rely on them will only get worse.
Larry Niles, a wildlife biologist and expert on the environmental issues of the Delaware Bay, says there is an inherent contradiction in the way state and federal agencies view horseshoe crabs. Horseshoe crabs are not a protected species and therefore they don’t see them as valuable, he says.
“Yet they acknowledge that there’s a $500 billion industry for their blood, so they’re not worthless,” Niles says. “They’re actually one of the most valuable marine species on the East Coast.”
It remains to be seen if lawsuits and increasing pressure from the public and environmental groups will force state and federal agencies to more rigorously regulate and protect horseshoe crabs or promote the adoption of rFC. However, Phelan hopes eventually labs and other pharmaceutical industry players will recognize the benefits of rFC, both in terms of cost and reliability. Adopting rFC will benefit companies as well as horseshoe crabs, she says.
“It’s a win-win for any pharmaceutical company that adopts this technology because they are going to have better quality control, better scientific output,” Phelan says. “Also, their employees, their stakeholders, or shareholders will feel better since they’re doing the right thing for the ecosystem.”